Streptomyces bacteria present in a given soil habitat collectively have the genetic capabilities for synthesis of hundreds of different antibiotics. Individual streptomyces strains often secrete more than one type of antibiotic. Various strains of streptomyces therefore might be expected to be rich sources of enzymes which inactivate endogenous and exogenous antibiotics. We have proposed that certain R factor genes might have originated in streptomyces. Since streptomycin-secreting strains of streptomyces are widely distributed in soils, streptomyces in general should be good sources of streptomycin-inactivating enzymes. We have preliminary evidence that streptomycin 6-kinase occurs in most strains of streptomyces, presumably serving a function in detoxification, transport, biosynthesis, metabolism, or storage of streptomycin. The objective of this research is to study in various strains of streptomyces the detailed enzymology of inactivation, biosynthesis, metabolism, and transport of the streoptomycin family of antibiotics. Particular emphasis will be placed on characterization of diverse kinases acting on streptomycin derivatives and phosphatases acting on the respective mono- and diphosphorylated products. Knowledge concerning the enzymatic pathways involved in biosynthesis and inactivation of a given antibiotic can be utilized in rational approaches to (a) design of fermentation media for increased production, (b) mutant selection procedures for obtaining superior producing strains, and (c) directed biosynthesis of novel antibiotics which are resistant to enzymatic inactivation by target microorganisms.